The objective of the proposed research is to characterize the multiple pathways of the cellular uptake and the subsequent degradation of liposomes in the liver. The program is geared to utilize the technique of gamma ray perturbed angular correlation, the approach of liver perfusion, and other analytical methods to investigate the influence of liposome dose and liposome properties on the extent and the rate of cellular uptake and degradation of liposomes in the liver of a mouse. The focus is on studying various pathways which control the uptake and degradation of liposomes in the liver. The goal of the proposed research program will encompass the following specific aims: (1) To test the hypothesis that the rate and extent of release of liposome contents in the liver depend upon accessibility of liposomes to various cellular sites of degradation, namely, the nonlysosomal, extracellular degradation and the intrecellular degradation in Kupffer cells, endothelial cells, and parenchymal cells, respectively. (2) To study the influence of liposome dose and liposome properties on the potential multiple pathways of the celllular uptake and degradation of liposomes in the liver.